In order that an organ or tissue functions normally in a living body, cell deaths of a part of cells as well as cell differentiation and cell proliferation are required. Most of such physiological cell deaths proceed due to apoptosis of which mechanism is usually strictly controlled.
Apoptosis is characterized by changes representatively including nuclear condensation and fragmentation of cells undergoing apoptosis, condensation and the fragmentation of the cells themselves, the fragmentation in the nucleosome unit (about 180 bp) of chromosomal DNA in the cells and the like.
For instance, in the formation process of an adult nematode (C. elegans), there is observed a phenomenon such that 131 cells die at a certain time in a certain site. In a mammal, it has also been known that a normal life event is maintained by the death of a certain cell at a certain time in the course of the development. These cell deaths are considered to be caused by apoptosis accompanied with morphological changes of the cells and the DNA fragmentation. Concretely, it has been shown that the cell deaths play an important role in the morphological formation during an individual development, the maintenance of a tissue homeostasis and the elimination of unwanted or hazardous cells.
Currently, studies on molecular mechanisms of apoptosis have been progressed. For instance, the studies on the action mechanisms of caspase-activated DNase [caspase-activated DNase (CAD)] and its inhibiting factor ICAD (inhibitor of CAD) in apoptosis have been made by the group of Nagata et al. [see, for instance, Enari, M., Nature, 391, 43–50 (1998) or the like]. Concretely, it is deduced that apoptosis signal causes an activation of cysteine protease caspase, and the resulting activated caspase then acts on CAD/ICAD complex (inactive form) to generate an active form CAD, and the active form CAD allows to fragmentate DNA into nucleosome unit, thereby resulting in cell death. Here, since the CAD synthesized in vitro in the absence of ICAD possesses no DNA-degrading activity, it is shown that the ICAD possesses a chaperonin function and is indispensable for the generation of the active form CAD.
Recently, it has been shown that the apoptosis is induced by a cancer-associated gene such as p53 antioncogene, c-myc or ras, an anti-cancer agent; irradiation with an ultraviolet or radioactive ray; or a certain cytokine representatively including Fas ligand, and the association with the signal transduction of apoptosis or the association with various diseases have come to a matter of interest.
However, studies on a target molecule for efficiently controlling apoptosis have not been sufficiently made at present.